NEJM: Is chemotherapy necessary for low-risk thyroid cancer?

Thyroid cancer is the most common tumor in the neck, and its detection rate has been on the rise in recent years

To reduce the risk of tumor recurrence, radionuclides (iodine-131) are also usually used after thyroidectomy to destroy remaining thyroid tissue and remove any remaining thyroid cancer cells, but this radiation therapy may take the patient for a period of time

Currently, there is a consensus that radioactive iodine therapy is not required for patients with single-focal microcarcinoma (diameter ≤10 mm), but whether radioactive iodine therapy is required for other low-risk thyroid cancer patients remains controversial

Recently, the University of Paris-Saclay published the results of a large randomized controlled clinical trial in the New England Journal of Medicine [5] (ESTIMABL2, NCT01837745)

If the results of this multicenter clinical trial are consistent with those of another similar multicenter clinical trial [6] (completed, data analysis), the results of this multicenter clinical trial will further optimize postoperative radioactive iodine therapy for thyroid cancer choice of indications

Inclusion criteria for this clinical study, called ESTIMABL2, were: pathologically proven differentiated thyroid cancer (papillary, follicular, or eosinophilic thyroid cancer), multifocal pT1a tumors (each lesion ≤1 cm in diameter, longest tumor In adult patients with a sum of diameters ≤2 cm) or pT1b tumors (1 cm < tumor diameter ≤2 cm), regional lymph node involvement or regional lymph node metastasis cannot be assessed due to no neck dissection and no extrathyroidal invasion

The Leboulleux team randomly divided the enrolled patients into a radiotherapy group (RT group, 1.

The non-inferiority design of this study was to evaluate the non-RT group for functional events (foci of extrathyroid radioactive iodine uptake on whole body scan or SPECT, RT only), structural events (neck ultrasound) with suspicious mass and biopsy cytology ) and biochemical events (abnormal thyroglobulin or thyroglobulin antibody levels) at an event-free rate (noninferiority definition: no functional, structural, biochemical events) not lower than RT

Finally, 776 patients from 35 centers in France were included in the cohort

Among the 730 evaluable patients with complete follow-up data, the non-functional, structural, and biological event rates were 95.

Specifically, an outcome event occurred in 16 of 367 patients (4.

A total of 14 patients (4 in the no-radiotherapy group and 10 in the radiotherapy group) received additional treatment (surgery, radioactive iodine, or both) during the 3-year follow-up period, and the remaining patients received no additional treatment during the follow-up period

Next, the researchers assessed the quality of life of the patients in both groups

The incidence of salivary or lacrimal gland dysfunction was similar between the two groups at all time points, but the incidence of lacrimal gland dysfunction was higher in the RT group after 2 months of enrollment

The researchers also looked for predictors of functional, structural and biochemical events through univariate analysis

The analysis found functional, structural, and biochemical events in patients with tumors less than 14 mm in diameter and postoperative serum thyroglobulin levels above the cutoff value
.
The risk of an event occurring is higher
.

Finally, to understand whether there was a difference in tumor molecular pathology between patients with an outcome event (case group) and patients without an outcome event (control group), the researchers performed molecular pathology testing on 90 tumor samples and found that tumor samples had BRAF mutations, and 14 tumor samples had RAS Mutation, 6 tumor specimens developed tumorigenic fusion
.

There was no significant difference in the frequency of BRAF gene mutation between the case group (61.
5%) and the control group (53.
1%), and other mutations had no significant difference between the groups
.

It is worth noting that in previous studies involving patients with low-risk thyroid cancer, tumor recurrence mostly occurred in the first 5 years of follow-up, while this study only followed patients for 3 years, it would be more difficult to have longer follow-up data.
But more convincing
.

However, the flaws do not hide the beauty
.
In this multicenter, randomized, controlled trial involving patients with low-risk differentiated thyroid cancer, researchers demonstrated for the first time that patients who did not receive radioactive iodine after thyroidectomy had no worse prognosis than those who received radioactive iodine
.
This provides an opportunity to get rid of the hassle and toxic side effects of radioactive iodine therapy
.

references

1.
Kim J, Gosnell JE, Roman SA: Geographic influences in the global rise of thyroid cancer.
Nat Rev Endocrinol 2020, 16(1):17-29.

2.
Megwalu UC, Moon PK: Thyroid Cancer Incidence and Mortality Trends in the United States: 2000-2018.
Thyroid 2022.

3.
Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M et al: 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer : The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer.
Thyroid 2016, 26(1):1-133.

4.
Verburg FA, Flux G, Giovanella L, van Nostrand D, Muylle K, Luster M: Differentiated thyroid cancer patients potentially benefitting from postoperative Mol I-131 therapy: a review of the literature of the past decade.
Eur J Nucl Med Imaging 2020, 47(1):78-83.

5.
Leboulleux S, Bournaud C, Chougnet CN, Zerdoud S, Al Ghuzlan A, Catargi B, Do Cao C, Kelly A, Barge ML, Lacroix L et al: Thyroidectomy without Radioiodine in Patients with Low-Risk Thyroid Cancer.
N Engl J Med 2022, 386(10):923-932.

6.
Mallick U, Harmer C, Hackshaw A, Moss L, Io NTMG: Iodine or Not (IoN) for low-risk differentiated thyroid cancer: the next UK National Cancer Research Network randomised trial following HiLo.
Clin Oncol (R Coll Radiol) 2012, 24(3):159-161.